Platinum Conjugates for Improved Tumor Accumulation

The invention includes compositions and methods for directly conjugating a passive targeting moiety onto platinum-based chemotherapeutics as a strategy to reduce the high toxicity associated with current platinum drug formulations. These platinum conjugates displayed enhanced permeability and retention, increased tumor suppression, and reduced toxicity compared to their unconjugated counterparts. Preliminary studies also revealed that the platinum conjugates were able to be administered at doses which were 2-3 fold higher than unconjugated platinum agents while demonstrating similar or reduced toxicity.

 

Stage of Development

 

In vitro data: Feasibility studies have been completed to validate the direct conjugation strategy. To date, we have demonstrated successful conjugation using four different targeting moieties, although we think this conjugation strategy could be effective for a variety of similar targeting moieties.

In vivo data: Preliminary mouse studies revealed that one of the platinum conjugates was particularly effective at suppressing tumor growth while displaying less overall toxicity than its unconjugated derivative when intravenously administered to mice bearing colon tumors.

 

Competitive Landscape

 

Platinum agents are one of the most commonly used chemotherapy drugs for cancer treatment. Despite their huge success in the clinic, these agents are not devoid of drawbacks including severe side effects due to dose-related toxicity and the emergence of drug resistance. These challenges have led to the development of various scaffolds and conjugation strategies to improve the delivery of platinum-based chemotherapeutics. However, majority of these strategies involve the encapsulation of platinum compounds in nanotubes, liposomes, biodegradable proteins, or other polymers. While these conjugation strategies are seemingly effective, they are more complicated to manufacture and present additional barriers and challenges for translation to clinical use. Our invention aims to address these limitations by providing a direct conjugation strategy that is simple to manufacture and less toxic than the current platinum compounds on the market.

 

Competitive Advantages       

 

•       Increased anti-tumor efficacy

•       Reduced toxicity

•       Simple conjugation strategy

 

Patent Information:
Licensing Contact
Paige Glumac
pglumac@houstonmethodist.org

Inventors:
Haifa Shen
Dongfang Yu
Yongbin Liu